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Clearance of persistent hepatitis C virus infection in humanized mice using a claudin-1-targeting monoclonal antibody

(2015) NATURE BIOTECHNOLOGY. 33(5). p.549-U169
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Abstract
Hepatitis C virus (HCV) infection is a leading cause of liver cirrhosis and cancer(1). Cell entry of HCV2 and other pathogens(3-5) is mediated by tight junction (TJ) proteins, but successful therapeutic targeting of TJ proteins has not been reported yet. Using a human liver-chimeric mouse model(6), we show that a monoclonal antibody specific for the TJ protein claudin-1 (ref. 7) eliminates chronic HCV infection without detectable toxicity. This antibody inhibits HCV entry, cell-cell transmission and virus-induced signaling events. Antibody treatment reduces the number of HCV-infected hepatocytes in vivo, highlighting the need for de novo infection by means of host entry factors to maintain chronic infection. In summary, we demonstrate that an antibody targeting a virus receptor can cure chronic viral infection and uncover TJ proteins as targets for antiviral therapy.
Keywords
CLAUDIN-1, EXPRESSION, CD81, RECEPTOR, IN-VIVO, CELL ENTRY, HUMAN LIVER, ENTRY FACTORS, HUMAN HEPATOCYTES, NEUTRALIZING ANTIBODIES

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Citation

Please use this url to cite or link to this publication:

Chicago
Mailly, Laurent, Fei Xiao, Joachim Lupberger, Garrick K Wilson, Philippe Aubert, François HT Duong, Diego Calabrese, et al. 2015. “Clearance of Persistent Hepatitis C Virus Infection in Humanized Mice Using a Claudin-1-targeting Monoclonal Antibody.” Nature Biotechnology 33 (5): 549–U169.
APA
Mailly, L., Xiao, F., Lupberger, J., Wilson, G. K., Aubert, P., Duong, F. H., Calabrese, D., et al. (2015). Clearance of persistent hepatitis C virus infection in humanized mice using a claudin-1-targeting monoclonal antibody. NATURE BIOTECHNOLOGY, 33(5), 549–U169.
Vancouver
1.
Mailly L, Xiao F, Lupberger J, Wilson GK, Aubert P, Duong FH, et al. Clearance of persistent hepatitis C virus infection in humanized mice using a claudin-1-targeting monoclonal antibody. NATURE BIOTECHNOLOGY. 2015;33(5):549–U169.
MLA
Mailly, Laurent, Fei Xiao, Joachim Lupberger, et al. “Clearance of Persistent Hepatitis C Virus Infection in Humanized Mice Using a Claudin-1-targeting Monoclonal Antibody.” NATURE BIOTECHNOLOGY 33.5 (2015): 549–U169. Print.
@article{6717062,
  abstract     = {Hepatitis C virus (HCV) infection is a leading cause of liver cirrhosis and cancer(1). Cell entry of HCV2 and other pathogens(3-5) is mediated by tight junction (TJ) proteins, but successful therapeutic targeting of TJ proteins has not been reported yet. Using a human liver-chimeric mouse model(6), we show that a monoclonal antibody specific for the TJ protein claudin-1 (ref. 7) eliminates chronic HCV infection without detectable toxicity. This antibody inhibits HCV entry, cell-cell transmission and virus-induced signaling events. Antibody treatment reduces the number of HCV-infected hepatocytes in vivo, highlighting the need for de novo infection by means of host entry factors to maintain chronic infection. In summary, we demonstrate that an antibody targeting a virus receptor can cure chronic viral infection and uncover TJ proteins as targets for antiviral therapy.},
  author       = {Mailly, Laurent and Xiao, Fei and Lupberger, Joachim and Wilson, Garrick K and Aubert, Philippe and Duong, Fran\c{c}ois HT and Calabrese, Diego and Leboeuf, C{\'e}line and Fofana, Isabel and Thumann, Christine and Bandiera, Simonetta and L{\"u}rgehetmann, Marc and Volz, Tassilo and Davis, Christopher and Harris, Helen J and Mee, Christopher J and Girardi, Erika and Chane-Woon-Ming, B{\'e}atrice and Ericsson, Maria and Fletcher, Nicola and Bartenschlager, Ralf and Pessaux, Patrick and Vercauteren, Koen and Meuleman, Philip and Villa, Pascal and Kaderali, Lars and Pfeffer, S{\'e}bastien and Heim, Markus H and Neunlist, Michel and Zeisel, Mirjam B and Dandri, Maura and McKeating, Jane A and Robinet, Eric and Baumert, Thomas F},
  issn         = {1087-0156},
  journal      = {NATURE BIOTECHNOLOGY},
  language     = {eng},
  number       = {5},
  pages        = {549--U169},
  title        = {Clearance of persistent hepatitis C virus infection in humanized mice using a claudin-1-targeting monoclonal antibody},
  url          = {http://dx.doi.org/10.1038/nbt.3179},
  volume       = {33},
  year         = {2015},
}

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